Kotin R M, Linden R M, Berns K I
Molecular Hematology Branch, National Institutes of Health, Bethesda, MD 20892.
EMBO J. 1992 Dec;11(13):5071-8. doi: 10.1002/j.1460-2075.1992.tb05614.x.
The human parvovirus, adeno-associated virus (AAV), has been shown to integrate preferentially into human chromosome 19 q13.3-qter. The human target sequence for AAV integration (AAVS1) was cloned and sequenced. By analysis of the proviral junctions it was determined that integration of the AAV DNA occurred via a non-homologous recombination pathway although there were either four or five identical nucleotides at the junctions. Integration was a multistep, concerted process that resulted in cellular sequence rearrangements. The sequence of the integration locus was analyzed for possible recombination signals. Direct repeats at a much greater than random occurrence were found distributed non-uniformly throughout the AAVS1 sequence. A CpG island containing transcription factor binding site elements is suggestive of a TATA-less promoter. Evidence for transcriptional activity was provided by PCR amplification of reverse transcribed RNA.
人类细小病毒，腺相关病毒（AAV），已被证明优先整合到人类19号染色体q13.3 - qter区域。克隆并测序了AAV整合的人类靶序列（AAVS1）。通过对前病毒连接点的分析确定，尽管连接点处存在四个或五个相同的核苷酸，但AAV DNA的整合是通过非同源重组途径发生的。整合是一个多步骤的协同过程，导致细胞序列重排。分析了整合位点的序列以寻找可能的重组信号。发现分布在AAVS1序列中且出现频率远高于随机水平的直接重复序列。一个含有转录因子结合位点元件的CpG岛提示存在一个无TATA框的启动子。逆转录RNA的PCR扩增提供了转录活性的证据。
